Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

Forward Programming of Pluripotent Stem Cells to Neurons

Author(s): Jinchao Gu, Brett Cromer and Huseyin Sumer*

Volume 21, Issue 1, 2021

Published on: 21 April, 2020

Page: [5 - 14] Pages: 10

DOI: 10.2174/1566524020666200421115251

Price: $65

Abstract

Pluripotent stem cells (PSCs) are powerful tools for studying developmental biology and neuronal diseases. Conventional differentiation protocols require several intermediate states and different culture conditions, inefficiently generating mixed subtypes of neuronal cells with immature characteristics. Direct programming of PSCs by forced expression of neuronal transcription factors has shown rapid cell fate determination with high purity as it can bypass sequential developmental steps that traditional culture requires. In this review, we focus on neuronal differentiation from PSCs to specific subtypes by various transcription factors. Furthermore, the potential applications and limitations of this novel technology are discussed.

Keywords: Programming, Embryonic stem cells, Pluripotent stem cells, Neuronal differentiation, Neurons, Transcription factor.

[1]
Romito A, Cobellis G. Pluripotent Stem Cells: Current Understanding and Future Directions. Stem Cells Int 2016; 20169451492
[http://dx.doi.org/10.1155/2016/9451492] [PMID: 26798367]
[2]
He Q, Li J, Bettiol E, Jaconi ME. Embryonic Stem Cells: New Possible Therapy for Degenerative Diseases That Affect Elderly People. J Gerontol Series A 2003; 58(3): M279-87.
[3]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[4]
Oh Y, Jang J. Directed Differentiation of Pluripotent Stem Cells by Transcription Factors. Mol Cells 2019; 42(3): 200-9.
[PMID: 30884942]
[5]
Zhang Y, Pak C, Han Y, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 2013; 78(5): 785-98.
[http://dx.doi.org/10.1016/j.neuron.2013.05.029] [PMID: 23764284]
[6]
Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 2009; 27(3): 275-80.
[http://dx.doi.org/10.1038/nbt.1529] [PMID: 19252484]
[7]
Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 2010; 463(7284): 1035-41.
[http://dx.doi.org/10.1038/nature08797] [PMID: 20107439]
[8]
Pang ZP, Yang N, Vierbuchen T, et al. Induction of human neuronal cells by defined transcription factors. Nature 2011; 476(7359): 220-3.
[http://dx.doi.org/10.1038/nature10202] [PMID: 21617644]
[9]
Thoma EC, Wischmeyer E, Offen N, et al. Ectopic expression of neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons. PLoS One 2012; 7(6)e38651
[http://dx.doi.org/10.1371/journal.pone.0038651] [PMID: 22719915]
[10]
Ho S-M, Hartley BJ, Tcw J, et al. Rapid Ngn2-induction of excitatory neurons from hiPSC-derived neural progenitor cells. Methods 2016; 101: 113-24.
[http://dx.doi.org/10.1016/j.ymeth.2015.11.019] [PMID: 26626326]
[11]
Busskamp V, Lewis NE, Guye P, et al. Rapid neurogenesis through transcriptional activation in human stem cells. Mol Syst Biol 2014; 10(11): 760.
[http://dx.doi.org/10.15252/msb.20145508] [PMID: 25403753]
[12]
Matsushita M, Nakatake Y, Arai I, et al. Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors. Biochem Biophys Res Commun 2017; 490(2): 296-301.
[http://dx.doi.org/10.1016/j.bbrc.2017.06.039] [PMID: 28610919]
[13]
Chanda S, Ang CE, Davila J, et al. Generation of induced neuronal cells by the single reprogramming factor ASCL1. Stem Cell Reports 2014; 3(2): 282-96.
[http://dx.doi.org/10.1016/j.stemcr.2014.05.020] [PMID: 25254342]
[14]
Castro DS, Martynoga B, Parras C, et al. A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets. Genes Dev 2011; 25(9): 930-45.
[http://dx.doi.org/10.1101/gad.627811] [PMID: 21536733]
[15]
Yang N, Chanda S, Marro S, et al. Generation of pure GABAergic neurons by transcription factor programming. Nat Methods 2017; 14(6): 621-8.
[http://dx.doi.org/10.1038/nmeth.4291] [PMID: 28504679]
[16]
Sun AX, Yuan Q, Tan S, et al. Direct Induction and Functional Maturation of Forebrain GABAergic Neurons from Human Pluripotent Stem Cells. Cell Rep 2016; 16(7): 1942-53.
[http://dx.doi.org/10.1016/j.celrep.2016.07.035] [PMID: 27498872]
[17]
] Knox BAa. Biology : an Australian focusLadiges PYa, Evans BKa, St Robert Ja, Eds. North Ryde, N.S.W. : McGraw-Hill education 2014..
[18]
Yoo AS, Sun AX, Li L, et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 2011; 476(7359): 228-31.
[http://dx.doi.org/10.1038/nature10323] [PMID: 21753754]
[19]
Yuan F, Chen X, Fang K-H, et al. Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6. eLife 2018; 7: e373-82.
[http://dx.doi.org/10.7554/eLife.37382] [PMID: 30251953]
[20]
Poulin J-F, Zou J, Drouin-Ouellet J, Kim KY, Cicchetti F, Awatramani RB. Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling. Cell Rep 2014; 9(3): 930-43.
[http://dx.doi.org/10.1016/j.celrep.2014.10.008] [PMID: 25437550]
[21]
Chinta SJ, Andersen JK. Dopaminergic neurons. Int J Biochem Cell Biol 2005; 37(5): 942-6.
[http://dx.doi.org/10.1016/j.biocel.2004.09.009] [PMID: 15743669]
[22]
Theka I, Caiazzo M, Dvoretskova E, et al. Rapid generation of functional dopaminergic neurons from human induced pluripotent stem cells through a single-step procedure using cell lineage transcription factors. Stem Cells Transl Med 2013; 2(6): 473-9.
[http://dx.doi.org/10.5966/sctm.2012-0133] [PMID: 23658252]
[23]
Chu Y, Le W, Kompoliti K, Jankovic J, Mufson EJ, Kordower JH. Nurr1 in Parkinson’s disease and related disorders. J Comp Neurol 2006; 494(3): 495-514.
[http://dx.doi.org/10.1002/cne.20828] [PMID: 16320253]
[24]
Cai J, Donaldson A, Yang M, German MS, Enikolopov G, Iacovitti L. The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson’s disease model. Stem Cells 2009; 27(1): 220-9.
[http://dx.doi.org/10.1634/stemcells.2008-0734] [PMID: 18832589]
[25]
Xue Y, Zhan X, Sun S, et al. Synthetic mRNAs Drive Highly Efficient iPS Cell Differentiation to Dopaminergic Neurons. Stem Cells Transl Med 2019; 8(2): 112-23.
[http://dx.doi.org/10.1002/sctm.18-0036] [PMID: 30387318]
[26]
Sagal J, Zhan X, Xu J, et al. Proneural transcription factor Atoh1 drives highly efficient differentiation of human pluripotent stem cells into dopaminergic neurons. Stem Cells Transl Med 2014; 3(8): 888-98.
[http://dx.doi.org/10.5966/sctm.2013-0213] [PMID: 24904172]
[27]
Novitch BG, Wichterle H, Jessell TM, Sockanathan S. A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification. Neuron 2003; 40(1): 81-95.
[http://dx.doi.org/10.1016/j.neuron.2003.08.006] [PMID: 14527435]
[28]
Hester ME, Murtha MJ, Song S, et al. Rapid and efficient generation of functional motor neurons from human pluripotent stem cells using gene delivered transcription factor codes. Mol Ther 2011; 19(10): 1905-12.
[http://dx.doi.org/10.1038/mt.2011.135] [PMID: 21772256]
[29]
Goto K, Imamura K, Komatsu K, et al. Simple Derivation of Spinal Motor Neurons from ESCs/iPSCs Using Sendai Virus Vectors. Mol Ther Methods Clin Dev 2017; 4: 115-25.
[http://dx.doi.org/10.1016/j.omtm.2016.12.007] [PMID: 28344997]
[30]
Lee S, Cuvillier JM, Lee B, Shen R, Lee JW, Lee S-K. Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs. Proc Natl Acad Sci USA 2012; 109(9): 3383-8.
[http://dx.doi.org/10.1073/pnas.1114515109] [PMID: 22343290]
[31]
Goparaju SK, Kohda K, Ibata K, et al. Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors. Sci Rep 2017; 7: 42367.
[http://dx.doi.org/10.1038/srep42367] [PMID: 28205555]
[32]
Tcw J, Wang M, Pimenova AA, et al. An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells. Stem Cell Reports 2017; 9(2): 600-14.
[http://dx.doi.org/10.1016/j.stemcr.2017.06.018] [PMID: 28757165]
[33]
Canals I, Ginisty A, Quist E, et al. Rapid and efficient induction of functional astrocytes from human pluripotent stem cells. Nat Methods 2018; 15(9): 693-6.
[http://dx.doi.org/10.1038/s41592-018-0103-2] [PMID: 30127505]
[34]
Caiazzo M, Giannelli S, Valente P, et al. Direct conversion of fibroblasts into functional astrocytes by defined transcription factors. Stem Cell Reports 2015; 4(1): 25-36.
[http://dx.doi.org/10.1016/j.stemcr.2014.12.002] [PMID: 25556566]
[35]
Brenner M, Goldman JE, Quinlan RA, Messing A. Alexander Disease: A Genetic Disorder of AstrocytesAstrocytes in (Patho)Physiology of the Nervous System Boston, MA. Springer US 2009; pp. 591-648.
[http://dx.doi.org/10.1007/978-0-387-79492-1_24]
[36]
Chuang J-H, Tung L-C, Lin Y. Neural differentiation from embryonic stem cells in vitro: An overview of the signaling pathways. World J Stem Cells 2015; 7(2): 437-47.
[http://dx.doi.org/10.4252/wjsc.v7.i2.437] [PMID: 25815127]
[37]
Yamamizu K, Sharov AA, Piao Y, et al. Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines. Sci Rep 2016; 6(1): 25667.
[http://dx.doi.org/10.1038/srep25667] [PMID: 27150017]
[38]
Osten P, Dittgen T, Licznerski P. Lentivirus-Based Genetic Manipulations in Neurons In Vivo. Boca Raton, FL: CRC Press/Taylor & Francis 2006.
[39]
Lu X, Huang W. PiggyBac mediated multiplex gene transfer in mouse embryonic stem cell. PLoS One 2014; 9(12)e115072
[http://dx.doi.org/10.1371/journal.pone.0115072] [PMID: 25517991]
[40]
Zhao S, Jiang E, Chen S, et al. PiggyBac transposon vectors: the tools of the human gene encoding. Transl Lung Cancer Res 2016; 5(1): 120-5.
[PMID: 26958506]
[41]
Mansouri M, Bellon-Echeverria I, Rizk A, et al. Highly efficient baculovirus-mediated multigene delivery in primary cells. Nat Commun 2016; 7: 11529.
[http://dx.doi.org/10.1038/ncomms11529] [PMID: 27143231]
[42]
Little D, Ketteler R, Gissen P, Devine MJ. Using stem cell-derived neurons in drug screening for neurological diseases. Neurobiol Aging 2019; 78: 130-41.
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.008] [PMID: 30925301]
[43]
Tojima T, Yamane Y, Takahashi M, Ito E. Acquisition of neuronal proteins during differentiation of NG108-15 cells. Neurosci Res 2000; 37(2): 153-61.
[http://dx.doi.org/10.1016/S0168-0102(00)00110-3] [PMID: 10867177]
[44]
Seidman KJN, Barsuk JH, Johnson RF, Weyhenmeyer JA. Differentiation of NG108-15 neuroblastoma cells by serum starvation or dimethyl sulfoxide results in marked differences in angiotensin II receptor subtype expression. J Neurochem 1996; 66(3): 1011-8.
[http://dx.doi.org/10.1046/j.1471-4159.1996.66031011.x] [PMID: 8769861]
[45]
Ahfeldt T, Litterman NK, Rubin LL. Studying human disease using human neurons. Brain Res 2017; 1656: 40-8.
[http://dx.doi.org/10.1016/j.brainres.2016.03.051] [PMID: 27060768]
[46]
Daniszewski M, Crombie DE, Henderson R, et al. Automated Cell Culture Systems and Their Applications to Human Pluripotent Stem Cell Studies. SLAS Technol 2018; 23(4): 315-25.
[http://dx.doi.org/10.1177/2472630317712220] [PMID: 28574793]
[47]
Engle SJ, Blaha L, Kleiman RJ. Best Practices for Translational Disease Modeling Using Human iPSC-Derived Neurons. Neuron 2018; 100(4): 783-97.
[http://dx.doi.org/10.1016/j.neuron.2018.10.033] [PMID: 30465765]
[48]
Eiraku M, Takata N, Ishibashi H, et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 2011; 472(7341): 51-6.
[http://dx.doi.org/10.1038/nature09941] [PMID: 21475194]
[49]
Jung-Klawitter S, Opladen T. Induced pluripotent stem cells (iPSCs) as model to study inherited defects of neurotransmission in inborn errors of metabolism. J Inherit Metab Dis 2018; 41(6): 1103-16.
[http://dx.doi.org/10.1007/s10545-018-0225-9] [PMID: 29980968]
[50]
Krencik R, Seo K, van Asperen JV, et al. Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes. Stem Cell Reports 2017; 9(6): 1745-53.
[http://dx.doi.org/10.1016/j.stemcr.2017.10.026] [PMID: 29198827]
[51]
Tekin H, Simmons S, Cummings B, et al. Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons. Nat Biomed Eng 2018; 2(7): 540-54.
[http://dx.doi.org/10.1038/s41551-018-0219-9] [PMID: 30271673]
[52]
Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang S-C. Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat Protoc 2013; 8(9): 1670-9.
[http://dx.doi.org/10.1038/nprot.2013.106] [PMID: 23928500]
[53]
Cao S-Y, Hu Y, Chen C, et al. Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule Sci Rep 2017; 7(1): 3282
[http://dx.doi.org/10.1038/s41598-017-03519-w ] [PMID: 28607372]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy